Translating bacteriophage-derived depolymerases into antibacterial therapeutics: Challenges and prospects

Wang, Honglan; Liu, Yannan; Bai, Changqing; Leung, Sharon Shui Yee

doi:10.1016/j.apsb.2023.08.017

Cited by 14 publications

(4 citation statements)

References 97 publications

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“…Purified TSPs have also demonstrated promising potential as therapeutics or diagnostic tools (Wang et al . 2023).…”

Section: Discussionmentioning

confidence: 99%

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Agtrevirus phage AV101 infect diverse extended spectrum β-lactamaseE. coliby recognizing four different O-antigens

Sørensen,

Kalmar,

Lutz

et al. 2023

Preprint

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Bacteriophages in theAgtrevirusgenus are known for expressing multiple tail spike proteins (TSPs), but little is known about their genetic diversity and host recognition apart from their ability to infect diverseEnterobacteriaceaespecies. Here we aim to determine the genetic differences that may account for the diverse host ranges ofAgrevirusphages. We performed comparative genomics of 14Agtrevirusand identified only a few genetic differences including genes involved in nucleotide metabolism. Most notably was the diversity of thetspgene cluster, specifically in the receptor binding domains that were unique among most of the phages. We further characterized agtrevirus AV101 infecting nine diverse Extended Spectrum β-lactamase (ESBL)E. coliand demonstrated that this phage encoded four unique TSPs amongAgtrevirus. Purified TSPs formed translucent zones and inhibited AV101 infection of specific hosts, demonstrating that TSP1, TSP2, TSP3, and TSP4 recognize O8, O82, O153, and O159 O-antigens of ESBLE. coli, respectively. BLASTp analysis showed that the receptor binding domain of TSP1, TSP2, TSP3 and TSP4 are similar to TSPs encoded byE. coliprophages and distant related virulent phages. Thus,Agtrevirusmay have gained their receptor binding domains by recombining with prophages or virulent phages. Overall, combining bioinformatic and biological data expands the understanding of TSP host recognition ofAgtrevirusand give new insight into the origin and acquisition of receptor binding domains ofAckermannviridaephages.One sentence summaryAgtrevirus phage AV101 express four unique tail spike proteins that recognize different O-antigens of Extended Spectrum β-Lactamase producingE. coli.

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“…Purified TSPs have also demonstrated promising potential as therapeutics or diagnostic tools (Wang et al . 2023).…”

Section: Discussionmentioning

confidence: 99%

“…Purified TSPs have also demonstrated promising potential as therapeutics or diagnostic tools (Wang et al 2023). For instance, oral administration of purified TSP of Lederbergvirus phage P22 dramatically decreased Salmonella colonization in the chicken gut and reduced penetration into internal organs (Waseh et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Agtrevirus phage AV101 infect diverse extended spectrum β-lactamaseE. coliby recognizing four different O-antigens

Sørensen,

Kalmar,

Lutz

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Purified TSPs have also demonstrated promising potential as therapeutics or diagnostic tools (Wang et al 2023 ). For instance, oral administration of purified TSP of Lederbergvirus phage P22 dramatically decreased Salmonella colonization in the chicken gut and reduced penetration into internal organs (Waseh et al 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Agtrevirus phage AV101 recognizes four different O-antigens infecting diverse E. coli

Sørensen,

Kalmár,

Lutz

et al. 2023

microLife

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Bacteriophages in the Agtrevirus genus are known for expressing multiple tail spike proteins (TSPs), but little is known about their genetic diversity and host recognition apart from their ability to infect diverse Enterobacteriaceae species. Here we aim to determine the genetic differences that may account for the diverse host ranges of Agrevirus phages. We performed comparative genomics of 14 Agtrevirus and identified only a few genetic differences including genes involved in nucleotide metabolism. Most notably was the diversity of the tsp gene cluster, specifically in the receptor binding domains that were unique among most of the phages. We further characterized agtrevirus AV101 infecting nine diverse Extended Spectrum β-lactamase (ESBL) E. coli and demonstrated that this phage encoded four unique TSPs among Agtrevirus. Purified TSPs formed translucent zones and inhibited AV101 infection of specific hosts, demonstrating that TSP1, TSP2, TSP3, and TSP4 recognize O8, O82, O153, and O159 O-antigens of E. coli, respectively. BLASTp analysis showed that the receptor binding domain of TSP1, TSP2, TSP3 and TSP4 are similar to TSPs encoded by E. coli prophages and distant related virulent phages. Thus, Agtrevirus may have gained their receptor binding domains by recombining with prophages or virulent phages. Overall, combining bioinformatic and biological data expands the understanding of TSP host recognition of Agtrevirus and give new insight into the origin and acquisition of receptor binding domains of Ackermannviridae phages.

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“…DPs can either be attached to a bacteriophage tail or exist in a free form, diffusing into the surrounding medium. DPs are classified into two groups: hydrolases (glycanases) or polysaccharide lyases [15,16]. These enzymes display a high degree of heterogeneity in terms of their substrate specificity, molecular weight, and sensitivity to physical and chemical factors.…”

Section: Introductionmentioning

confidence: 99%

Recombinant TP-84 Bacteriophage Glycosylase–Depolymerase Confers Activity against Thermostable Geobacillus stearothermophilus via Capsule Degradation

Łubkowska,

Sobolewski,

Adamowicz

et al. 2024

IJMS

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The TP-84 bacteriophage, which infects Geobacillus stearothermophilus strain 10 (G. stearothermophilus), has a genome size of 47.7 kilobase pairs (kbps) and contains 81 predicted protein-coding ORFs. One of these, TP84_26 encodes a putative tail fiber protein possessing capsule depolymerase activity. In this study, we cloned the TP84_26 gene into a high-expression Escherichia coli (E. coli) system, modified its N-terminus with His-tag, expressed both the wild type gene and His-tagged variant, purified the recombinant depolymerase variants, and further evaluated their properties. We developed a direct enzymatic assay for the depolymerase activity toward G. stearothermophilus capsules. The recombinant TP84_26 protein variants effectively degraded the existing bacterial capsules and inhibited the formation of new ones. Our results provide insights into the novel TP84_26 depolymerase with specific activity against thermostable G. stearothermophilus and its role in the TP-84 life cycle. The identification and characterization of novel depolymerases, such as TP84_26, hold promise for innovative strategies to combat bacterial infections and improve various industrial processes.

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Translating bacteriophage-derived depolymerases into antibacterial therapeutics: Challenges and prospects

Cited by 14 publications

References 97 publications

Agtrevirus phage AV101 infect diverse extended spectrum β-lactamaseE. coliby recognizing four different O-antigens

Agtrevirus phage AV101 infect diverse extended spectrum β-lactamaseE. coliby recognizing four different O-antigens

Agtrevirus phage AV101 recognizes four different O-antigens infecting diverse E. coli

Recombinant TP-84 Bacteriophage Glycosylase–Depolymerase Confers Activity against Thermostable Geobacillus stearothermophilus via Capsule Degradation

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